NOVOBIOCIN MODULATES COLCHICINE SENSITIVITY IN PARENTAL AND MULTIDRUG-RESISTANT B16 MELANOMA-CELLS

The effect of the antibiotic agent novobiocin on the sensitivity of me lanoma cells to colchicine and vinblastine was examined in drug-sensit ive and drug-resistant B16 melanoma cells. A cell line COL/R was selec ted for colchicine resistance. The COL/R cell line (resistant to 80 ng /ml colchicine) was found to possess the multidrug-resistant (MDR) phe notype. The cells were shown to be cross-resistant to vinblastine and Adriamycin and to overexpress P glycoprotein. P glycoprotein activity was assessed by using the rhodamine 123 accumulation test. Rhodamine a ccumulation was markedly decreased in COL/R cells as compared to the p arental B16 cells. Verapamil reversed drug resistance and increased rh odamine accumulation in COL/R cells. Novobiocin in combination with co lchicine or vinblastine synergistically inhibited the proliferation of parental B16 cells. In COL/R cells, novobiocin markedly decreased col chicine resistance and increased rhodamine accumulation. These data sh ow that novobiocin increases the sensitivity of both parental and MDR melanoma cells to microtubule-disrupting cytotoxic drugs.